Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

  • Authors:
    • Yukiya Narita
    • Shigenori Kadowaki
    • Toshiki Masuishi
    • Hiroya Taniguchi
    • Daisuke Takahari
    • Takashi Ura
    • Masashi Ando
    • Masahiro Tajika
    • Yasumasa Niwa
    • Tetsuya Eto
    • Hiroki Hara
    • Masako Asayama
    • Kensei Yamaguchi
    • Yasushi Yatabe
    • Kei Muro
  • View Affiliations

  • Published online on: June 19, 2017     https://doi.org/10.3892/ol.2017.6409
  • Pages: 2545-2551
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Abstract

There is currently no clinical data regarding the efficacy of trastuzumab treatment for the progression of human epidermal growth factor receptor 2 (HER2)‑positive advanced gastric cancer (AGC) occurring during trastuzumab-based chemotherapy. The aim of this study was to retrospectively examine the clinical benefits of trastuzumab for HER2‑positive AGC patients who progressed during first‑line trastuzumab‑based chemotherapy. Among the 108 patients treated with trastuzumab combined with fluoropyrimidine and cisplatin as first‑line therapy, 46 HER2‑positive AGC patients who received cytotoxic agents with or without trastuzumab subsequent to disease progression were included. Of these, the efficacy and safety outcomes of 26 patients who continued trastuzumab were compared with those of the 20 patients who discontinued trastuzumab. No difference in response rate (18.2 vs. 15.8%, P=1.00) was observed between the two groups. Progression‑free survival (PFS) time was numerically longer in the chemotherapy combination with trastuzumab group than in the chemotherapy combination without trastuzumab group (median, 4.0 vs. 2.3 months), with no significance [hazard ratio (HR), 0.63; P=0.14]. In the subset analysis, continuation of trastuzumab significantly improved PFS time in selected subgroups of patients with tumors exhibiting HER2 expression scores of 3+ (HR, 0.41; P=0.04), intestinal‑type histology (HR, 0.32; P<0.01), and a first PFS time of >6 months (HR, 0.44; P=0.04). The survival times for the trastuzumab beyond progression (TBP) and non‑TBP groups were similar (HR, 1.06; P=0.88), with equivalent overall survival times in the subgroups with immunohistochemistry scores of 3+ (HR, 0.97; P=0.94), intestinal‑type histology (HR, 0.53; P=0.19), and a first PFS time of >6 months (HR, 0.62; P=0.31). There were no differences in the incidence rates of toxicity, including cardiac dysfunction, between the two groups. The study results suggest that selected HER2‑positive AGC patients may benefit from trastuzumab continuation during first progression, and further prospective studies are warranted.

References

1 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Glimelius B, Ekström K, Hoffman K, Graf W, Sjödén PO, Haglund U, Svensson C, Enander LK, Linné T, Sellström H and Heuman R: Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 8:163–168. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA and Rausch M: Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 72:37–41. 1993. View Article : Google Scholar : PubMed/NCBI

4 

Pyrhonen S, Kuitunen T, Nyandoto P and Kouri M: Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer. 71:587–591. 1995. View Article : Google Scholar : PubMed/NCBI

5 

Ajani JA, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, et al: Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: The V-325 Study Group. J Clin Oncol. 25:3205–3209. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J and Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom, : Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 358:36–46. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, et al: S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): A phase III trial. Lancet Oncol. 9:215–221. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, et al: Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): An open-label, phase 3 randomised controlled trial. Lancet Oncol. 15:78–86. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, et al: Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 31:4438–4444. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, et al: Salvage chemotherapy for pretreated gastric cancer: A randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 30:1513–1518. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Kim HS, Kim HJ, Kim SY, Kim TY, Lee KW, Baek SK, Kim TY, Ryu MH, Nam BH and Zang DY: Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: A meta-analysis. Ann Oncol. 24:2850–2854. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Aizawa M, Nagatsuma AK, Kitada K, Kuwata T, Fujii S, Kinoshita T and Ochiai A: Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population. Gastric Cancer. 17:34–42. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Barros-Silva JD, Leitão D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, Bento MJ, Santos L, Ferreira P, Rêgo S, et al: Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer. 100:487–493. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Takehana T, Kunitomo K, Kono K, Kitahara F, Iizuka H, Matsumoto Y, Fujino MA and Ooi A: Status of c-erbB-2 in gastric adenocarcinoma: A comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay. Int J Cancer. 98:833–837. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M and Ochiai A: Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep. 15:65–71. 2006.PubMed/NCBI

16 

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, et al: Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in asian populations: TyTAN-a randomized, phase III study. J Clin Oncol. 32:2039–2049. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Dai GH, Shi Y, Chen L, Lv YL and Zhong M: Trastuzumab combined with docetaxel-based regimens in previously treated metastatic gastric cancer patients with HER2 over-expression. Hepatogastroenterology. 59:2439–2444. 2012.PubMed/NCBI

19 

Jackisch C, Welslau M, Schoenegg W, Selbach J, Harich HD, Schröder J, Schmidt M, Göhler T, Eustermann H, Ringel R and Hinke A: Impact of trastuzumab treatment beyond disease progression for advanced/metastatic breast cancer on survival - results from a prospective, observational study in Germany. Breast. 23:603–608. 2014. View Article : Google Scholar : PubMed/NCBI

20 

von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, et al: Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: A German breast group 26/breast international group 03–05 study. J Clin Oncol. 27:1999–2006. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET and Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 5:649–655. 1982. View Article : Google Scholar : PubMed/NCBI

22 

NCCN Clinical Practice Guidelines in Oncology GC, Ver3. 2016.simplehttp://www.nccn.org/professionals/physician_gls/f_guidelines.aspOctober 30–2016

23 

Nishino M, Jagannathan JP, Ramaiya NH and Van den Abbeele AD: Revised RECIST guideline version 1.1: What oncologists want to know and what radiologists need to know. AJR Am J Roentgenol. 195:281–289. 2010. View Article : Google Scholar : PubMed/NCBI

24 

National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. simplehttps://evs.nci.nih.gov/ftp1/CTCAE/About.html

25 

Lee HE, Park KU, Yoo SB, Nam SK, do J Park, Kim HH and Lee HS: Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. Eur J Cancer. 49:1448–1457. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Hayashi M, Okumura Y, Osako T, Toyozumi Y, Arima N, Iwase H and Nishimura R: Time to first tumor progression as a predictor of efficacy of continued treatment with trastuzumab beyond progression in human epidermal growth factor receptor 2-positive metastatic breast cancer. Int J Clin Oncol. 16:694–700. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, et al: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol. 15:1224–1235. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ and Keefe D: Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 20:1215–1221. 2002. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
APA
Narita, Y., Kadowaki, S., Masuishi, T., Taniguchi, H., Takahari, D., Ura, T. ... Muro, K. (2017). Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer. Oncology Letters, 14, 2545-2551. https://doi.org/10.3892/ol.2017.6409
MLA
Narita, Y., Kadowaki, S., Masuishi, T., Taniguchi, H., Takahari, D., Ura, T., Ando, M., Tajika, M., Niwa, Y., Eto, T., Hara, H., Asayama, M., Yamaguchi, K., Yatabe, Y., Muro, K."Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer". Oncology Letters 14.2 (2017): 2545-2551.
Chicago
Narita, Y., Kadowaki, S., Masuishi, T., Taniguchi, H., Takahari, D., Ura, T., Ando, M., Tajika, M., Niwa, Y., Eto, T., Hara, H., Asayama, M., Yamaguchi, K., Yatabe, Y., Muro, K."Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer". Oncology Letters 14, no. 2 (2017): 2545-2551. https://doi.org/10.3892/ol.2017.6409